Factors associated with repeat symptomatic gonorrhea infections among men who have sex with men, Bangkok, Thailand Pattanasin S. 1, Luechai P. 1, Sriporn A. 1, Tongtoyai J. 1, Sukwicha W. 1, Kongpechsatit O. 1, Sirivongrangson P. 2, Holtz T.H. 1,3, Curlin M.E. 1,3, Dunne E.F. 1,3 1 Thailand Ministry of Public Health U.S. Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand; 2 Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand 3 Division of HIV/AIDS Prevention, U.S. Centers for Disease Control and Prevention, Georgia, U.S. Disclaimer The findings and views presented in this presentation are those of the author and do not necessarily represent those of the US Centers for Disease Control and Prevention.
Background Neisseria gonorrhea (NG) infection may increase the risk of HIV transmission 1-3 Gonococcal infection is concentrated in specific communities 4-5 and subgroups of men who have sex with men (MSM) are at high risk for gonorrhea infection3, 6, 7 Gonorrhea treatment is complicated by the ability of NG to develop resistance to antimicrobials, which limits the options for effective treatment and control of the disease4, 8, 9 Decreasing cephalosporin sensitivity among NG isolates was reported from the Gonococcal Isolate Surveillance Project, which found that MSM are vulnerable to the emerging threat of antimicrobial-resistant NG 10 Overall, around 6% of male and female patients receiving care in the UK were diagnosed with a repeat episode of NG within 6 months, and the majority (90%) of individuals diagnosed with NG reinfection were symptomatic 11 High prevalence of asymptomatic NG infection (7.5%), a predominance of rectal site infections and substantial diversity in correlates of infection between mucosal sites, were reported from MSM in Bangkok, Thailand 6
Objectives Among MSM enrolled in the Bangkok MSM Cohort Study (BMCS): To determine prevalence of rectal and urethral NG infection at baseline To describe incidence of symptomatic NG infection To evaluate baseline factors associated with repeat symptomatic NG infections during follow-up
Methods Study design: Prospective cohort study with 4-month interval for 3-5 years Study population Eligibility criteria: Thai male aged 18 years Residing in the Bangkok metropolitan area Reporting penetrative oral or anal sex with another man in the past 6 months Available to participate in a 4-month follow-up visit Recruitment methods: Convenient sampling from venues, Internet, a male sexual health clinic, and through outreach workers and friends
Methods Inclusion criteria for analysis : Men who had rectal and/or urethral specimens collected at enrollment Available for at least one follow-up visit for the calculation of incidence rate and factors associated with number of symptomatic NG infections during follow-up
At baseline: Methods Rectal swab, pharyngeal swab and first-void urine were collected for Chlamydia trachomatis (CT) and NG infection using nucleic acid amplification testing (NAAT) and Gram stain (for NG only) HIV testing Physical examination Assessment of behaviors using computer-assisted self-interview (ACASI) At follow-up visit: Symptomatic participants (i.e. men with urethral or anal discharge, urethral pain and rectal pain) were tested for NG and CT infection by NAAT and Gram stain from rectal or urethral specimens HIV testing, ACASI and physical examination At unscheduled visit: Physical examination if participants had signs or symptoms consistent with CT or NG infection
Methods CASI questionnaire on risk behaviors in the past 4 months administered every 4 months. Key questions included: Baseline: socio-demographic characteristics, history of HIV testing, history of diagnosis with Sexually Transmitted Infections Baseline and follow-up visit: use of recreational injectable/oral/inhalant drug to increase pleasure and/or sexual pleasure and sexual behaviors Men diagnosed with NG infection at any visit were treated using regimen recommended by the Thailand National Guidelines*: First line: 250 mg IM ceftriaxone Second line: 400 mg oral single dose *Routine empirical treatment for CT also recommended
Laboratory testing First-void urine and rectal swabs (Amplicor STD Swab Collection and Transport set) were tested for CT and NG by NAAT (Roche Amplicor, Roche Diagnostics, Branchburg, NJ, USA) and Gram stain (for NG only) HIV testing on oral fluid using OraQuick HIV-1/2 Rapid Test (OraSure Technologies, Bethlehem, PA, USA). If reactive, confirmed with three rapid tests on blood: Determine TM HIV-1/2 (Abbott Laboratories, Tokyo, Japan) or Determine TM HIV-1/2 (Alere Medical, Chiba, Japan) DoubleCheck TM II HIV 1&2 (Organics, Yavne, Israel), replaced after 02/2011 by SD-Bioline HIV-1/2 3.0 (Standard Diagnostics, Kyonggi-do, South-Korea) and replaced after 01/2012 by DBCheck Gold Ultra HIV-1/2 (Orgenics, Yavne, Israel) Capillus TM HIV-1/HIV-2 (Trinity Biotech, Jamestown, NY, USA), replaced after 11/2008 by Core TM HIV-1/2 (Birmingham, UK) Confirmation requires that all 3 tests are reactive
Statistical Analysis NG and CT prevalence at baseline was calculated as the proportion of men that tested positive by NAAT and/or intracellular Gram positive diplococci found by Gram stain, divided by the number of men tested We calculated symptomatic NG incidence per 100 person-years (PY) with exact Poisson 95% confidence interval (CI); follow-up time through December 2014 We determined factors associated with number of symptomatic NG infection using Poisson regression with robust standard error Time independent exposures (baseline) with p-value 0.10 were entered into multivariate model; likelihood ratio test was used to determine the final models We performed all analyses using STATA (Version 12, Stata Corp., College Station, Texas, USA)
At baseline: Results - Of 1,744 men enrolled during 2006-2010, 1 (0.1%) had no specimen collected and 1595 had both rectal and urethral specimen collected - Rectal NG prevalence was 6.1% (98/1595) - Urethral NG prevalence was 1.8% (29/1595) At follow-up visit: - 145 men were lost to follow-up (i.e., never returned for any follow-up visit after enrollment by September 30, 2014) - 1439 men were available for: one follow-up visit; no NG infection detected by NAAT/Gram stain at enrollment; and available for both rectal and urethral specimens, included in the longitudinal analysis
Table 1: Participants characteristics, N=1439 n % Median (IQR) Age (years) 26 (22, 30) 18-24 563 39.1 25 876 60.9 Education level Primary or less 34 2.4 Secondary/technical/vocational 736 51.1 University/higher 669 46.5 Sexual identity Results Bisexual 235 16.3 Transgender woman 45 3.1 Homosexual/gay 1154 80.2 Heterosexual 5 0.3 Enrollment period 2006-2008 1041 72.3 2009-2010 398 27.7
Results Repeat symptomatic NG infections during follow-up: - 119 men had symptomatic NG infection at any follow-up visit (incidence 2.1 per 100 Persons-Years: 95% CI 1.8-2.6) - Of 119 men with symptomatic NG infections, 81.5% (97/119) were urethral infections, 17.6% (21/119) were rectal infections and 0.8% (1/119) were both the urethra and the rectum - Repeat symptomatic NG infections were 40.3% (48/119) of participants: 68.7% (33/48) at the urethral site; 6.2% (3/48) at the rectal site; and 25.0% (12/48) were between the urethra and rectum - Of 48 men with repeat symptomatic NG infection, 50.0% (24/48) had 2 infections; 27.1% (13/48) had 3 infections; 8.3% (4/48) had 4 infections; 8.3% (4/48) had 5 infections; 2.1% (1/48) had 6 infections and 4.2% (2/48) had 7 infections - 13.4% (16/119) had repeat symptomatic NG infections within six months Median time between the first 2 infections was 294 days (IQR: 169-461 days)
Days between infections 0 500 1,000 1,500 1 2 3 4 5 6 7 Number of infection Figure 1: Number of Repeat Symptomatic Infections and Number of Days Preceding and Following Infection, Thai MSM enrolled in the BMCS 2006-2010, Bangkok, Thailand
Table 2: Risk factors significantly associated with number of symptomatic NG infections among a cohort of MSM participated in the BMCS, Bangkok, Thailand Characteristics Number of symptomatic NG infections* Period of enrollment Adjusted Incidence Rate Ratio (Adjusted IRR) 95% CI 2006-2008 2.5 1.5-4.3 2009-2010 Ref. History of HIV testing Ever and know the result 1.0 0.7-1.6 Ever but and do not know the result 2.8 1.2-6.7 Never tested History of previous STI diagnosis Ever 2.9 1.8-4.4 Never Prevalent CT infection at baseline Yes 2.2 1.4-3.6 No *NAAT or Gram stain Ref. Ref. Ref.
Conclusions Over a third of men with symptomatic NG infection had repeat infection Symptomatic repeat NG infections was associated with other STIs Specific prevention efforts might effectively be targeted to MSM who are diagnosed with NG and/or CT infection including - follow-up evaluation in 3 months for repeat NG and/or CT - increase access to same day HIV test result - strengthen post-hiv test counseling
Limitations Incidence rate reported here is likely an underestimation given we tested NG infection in men who experienced symptoms Many men may have had asymptomatic infection and might not have been captured We did not include dysuria in the definition of symptom We did not assess if the repeat symptomatic NG infection was reinfection or persistent infection
Recommendations Continued surveillance for NG and CT infection in at risk MSM is needed Routine culture and antimicrobial testing would be important to assess treatment failures as a reason for repeat infection Routine testing for cephalosporin susceptibility in MSM who develop repeat symptomatic NG infections are needed Routine follow-up after NG and CT needed to assess for repeat infections Expand coverage of HIV counseling and testing
Acknowledgments The authors are grateful to all the participants in the study, the Rainbow Sky Association of Thailand and outreach team, The M-CAB and the Silom Community Clinic @TropMed Silom Community Clinic staff (left), gram stain for rectal NG infection (middle) and gram stain for urethral NG infection (right)
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